6. Multi-Morbidity: Metabolic Disease to CVD, Cancer and Inflammation

Question 1

Who do chronic, non-communicable diseases affect?

Answer 1

People of all ages, nationalities and classes

Question 2

What do chronic, non-communicable diseases cause?

Answer 2

The greatest global share of disability and death - account for 60% of deaths worldwide

Question 3

Where do the majority of chronic, non-communicable diseases occur?

Answer 3

80% of chronic, non-communicable diseases occur in middle-income countries

Question 4

What are the 2 main risk factors for developing chronic, non-communicable diseases?

Answer 4

1. Smoking

2. Poor diet

Question 5

How does diabetes affect CVD relative risk?

Answer 5

• As progress from normal to pre-diabetes, RR of developing CVD doubles
• As progress from pre-diabetes to T2D, RR of developing CVD is triple that of normal

Question 6

What is hyperglycaemia thought to directly lead to?

What does this lead to?

Answer 6

• Atherosclerosis

- Leads to more complications (hypertension, CVD) which lead to progressive disability and ultimately death

Question 7

What is the relationship between obesity, insulin resistance and dyslipidemia?

Answer 7

• Central obesity is associated with an increase in free fatty acids (FFA) and insulin resistance (unclear whether increased FFA causes insulin resistance or vice versa)
• These 2 effects stimulate increased hepatic apolipoprotein B and hepatic lipase activity (catalyse removal of lipids from HDLs)
• This leads to hypertriglyceridemia, increased small, dense LDLs and decreased HDLs
• These abnormal lipid patterns increase risk of developing plaques in the CV system and therefore increases the risk of co-morbidity

Question 8

What is metabolic syndrome characterised by?

What is central to these effects?

Answer 8

• Complex dyslipidemia
• Endothelial dysfunction
• Systemic inflammation
• Disordered fibrinolysis
• Hypertension
• ATHEROSCLEROSIS
• Insulin resistance is central to all these effects and is therefore central to multi-morbidity

Question 9

What is the effect of metabolic disorders on some cancers?

Answer 9

The relative risk of some cancers (breast, uterine, bowel, kidney and oesophageal) are increased massively in individuals with metabolic disorders

Question 10

What are the 3 main ways how metabolic disorders can lead to cancer?

Answer 10

1. Oestrogen made by adipocytes can make cells proliferate faster in breast and womb (which is required for pregnancy), however after menopause this increases the risk of cancer
2. Insulin resistance and hyperinsulinemia affect the levels of growth factors which promote cell division. Excess fat can increase the levels of insulin and growth factors which promote uncontrolled cell proliferation
3. Large collections of adipocytes cause macrophages to gather around and activate immune response to tidy up surrounding area. Macrophages release cytokines which promote cell division

Question 11

How are T2D and cancer linked?

Answer 11

Animal models show that the insulin/IGF-1 signalling pathway is an ancient, conserved pathway that is fundamental to healthy ageing